[unreadable] Pituitary tumors rarely metastasize, but cause considerable morbidity and mortality. The peroxisome proliferator activating receptor-gamma (PPAR-y) is a nuclear receptor involved in fat and glucose homeostasis. Rosiglitazone, a PPAR-y ilgand, is approved for the management of diabetes mellitus. PPAR-y ligands inhibit prostate and breast cancer cell proliferation. The applicant recently demonstrated abundant PPAR-y expression in all of 41 pituitary tumors examined, in comparison to minimal PPAR- expression in 9 autopsy-derived normal human pituitaries. Rosiglitazone treatment of ACTH-, and non- secreting tumor cells led to G cell cycle arrest, decreased the percentage of S-phase cells, induced tumor cell apoptosis, and markedly inhibited pituitary tumor hormone production. They also observed that rosiglitazone treatment for glycemic control led to reduced urine cortisol levels in 4 of 5 rosiglitazone treated patients. [unreadable] [unreadable] This Phase 2 clinical trial will examine the potential therapeutic efficacy of rosiglitazone in treatment of human ACTH-secreting (Cushing's disease), and non-secreting pituitary tumors. In accordance with human subjects' guidelines, a total of 45 patients will participate in the study (Study 1 and 2: 30 patients with ACTH-secreting pituitary tumors; study 3: 15 patients with non-secreting tumors will be recruited). Consenting patients will undergo a detailed baseline historical, physical and biochemical evaluation, including measurement of the specific hormone(s), their pituitary tumor produces (e.g., patients with ACTH-secreting tumors will have their ACTH and cortisol levels measured), and a MRI assessment of the pituitary tumor size. Patients will commence treatment with PPAR-y ligand rosiglitazone, (8 mg by mouth, once per day) as approved for use in diabetes mellitus. Biochemical and endocrine examination will be re-evaluated weekly in study I (Cushing's) and monthly in study 2 (Cushing's), and radiological examination at baseline and at 6 months in study 2 (Cushing's), and baseline, 6, and 12 months in study 3 (non-functioning tumor) after rosiglitazone treatment. In the absence of side-effects or other contraindications, rosiglitazone therapy will continue for a total period of 6 weeks (study 1) or 6 months in the Cushing's patients and 12 months in patients with non-secreting tumors. Patient response will be determined by a statistical comparison of the follow-up assessments with baseline result. A complete response will be defined as normalization of urinary cortisol levels in the Cushing's patients, and disappearance of pituitary tumors in the non-secreting tumors from baseline. [unreadable] [unreadable]